Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis in <i>Trypanosoma cruzi</i>

• Main Authors: Rodolpho Ornitz Oliveira Souza, Marcell Crispim, Ariel Mariano Silber, Flávia Silva Damasceno
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Molecules
• Subjects: Chagas disease; <i>Trypanosoma cruzi</i>; azaserine; acivicin; glutamine metabolism; cell death
• Online Access: https://www.mdpi.com/1420-3049/25/7/1628

<i>Trypanosoma cruzi</i> is the aetiologic agent of Chagas disease, which affects people in the Americas and worldwide. The parasite has a complex life cycle that alternates among mammalian hosts and insect vectors. During its life cycle, <i>T. cruzi</i> passes through different environments and faces nutrient shortages. It has been established that amino acids, such as proline, histidine, alanine, and glutamate, are crucial to <i>T. cruzi</i> survival. Recently, we described that <i>T. cruzi</i> can biosynthesize glutamine from glutamate and/or obtain it from the extracellular environment, and the role of glutamine in energetic metabolism and metacyclogenesis was demonstrated. In this study, we analysed the effect of glutamine analogues on the parasite life cycle. Here, we show that glutamine analogues impair cell proliferation, the developmental cycle during the infection of mammalian host cells and metacyclogenesis. Taken together, these results show that glutamine is an important metabolite for <i>T. cruzi</i> survival and suggest that glutamine analogues can be used as scaffolds for the development of new trypanocidal drugs. These data also reinforce the supposition that glutamine metabolism is an unexplored possible therapeutic target.